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Gastric Inflammatory Prognostic Index (GIPI) in Patients with Metastatic Gastro-Esophageal Junction/Gastric Cancer Treated with PD-1/PD-L1 Immune Checkpoint Inhibitors

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Abstract

Background

Immune checkpoint inhibitors (ICIs) demonstrated improved overall survival (OS) in heavily pretreated unselected patients with metastatic gastro-esophageal junction (mGOJ)/gastric cancer (GC). Attempts to select patients based on programmed death-ligand 1 (PD-L1) expression appear to be suboptimal. A strong rationale suggests a prognostic role for inflammatory biomarkers for ICI-treated patients with mGOJ/GC.

Objective

Our objective was to assess whether inflammatory markers are associated with survival in ICI-treated patients with mGOJ/GC.

Methods

Ten inflammatory markers were retrospectively analyzed at baseline in 57 patients with mGOJ/GC with unknown PD-L1 status treated with second-line ICIs and correlated with OS. Selected variables were then analyzed in a multivariate Cox-regression model and used to build a GIPI nomogram.

Results

Neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) as continuous variables and albumin categorized as less than versus greater than 30 g/dL were the most significant predictors of OS and were used to build the GIPI nomogram. Nomogram-based lowest, mid-low, mid-high, and highest risk quartiles were associated with median OS (mOS) of 14.9, 7.1, 5.6, and 2.1 months, respectively (hazard ratio [HR] of highest vs. lowest risk 4.94; p = 0.0002). By optimally dichotomizing CRP and NLR, patients with one or more of the risk factors NLR > 6, CRP > 15 mg/L, and albumin < 30 g/dL (n = 29) had an mOS of 3.9 versus 14.2 months for patients with no risk factor (n = 28) (HR 2.48; p = 0.0015).

Conclusions

GIPI, combining NLR, CRP, and albumin, is the first inflammatory index with a significant prognostic value in patients with mOGJ/GC receiving ICIs. GIPI merits validation in independent cohorts and prospective clinical trials.

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Acknowledgements

Antonella Nardecchia carried out the present study within the Ph.D. program in Experimental and Systems Medicine, XXXII cycle, ‘Tor Vergata’ University of Rome. Cristina Morelli carried out the present study within the Ph.D. program in Experimental and Systems Medicine, XXXV cycle, ‘Tor Vergata’ University of Rome.

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Authors and Affiliations

  1. Medical Oncology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Viale Oxford, 81, 00133, Rome, Italy

    Vincenzo Formica, Cristina Morelli, Antonella Nardecchia, Jessica Lucchetti, Nicola Renzi & Mario Roselli

  2. Medical Oncology, Sarah Cannon Research Institute UK, London, UK

    Anna Patrikidou, Carmen Murias, Sabeeh Butt & Hendrik-Tobias Arkenau

  3. Department of Oncology, University College Hospital, 235 Euston Road, London, NW1 2BU, UK

    Kai-Keen Shiu

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  1. Vincenzo Formica
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Correspondence to Vincenzo Formica.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Vincenzo Formica, Cristina Morelli, Anna Patrikidou, Carmen Murias, Sabeeh Butt, Antonella Nardecchia, Jessica Lucchetti, Nicola Renzi, Kai-Keen Shiu, Mario Roselli, and Hendrik-Tobias Arkenau have no conflicts of interest that might be relevant to the contents of this manuscript.

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Formica, V., Morelli, C., Patrikidou, A. et al. Gastric Inflammatory Prognostic Index (GIPI) in Patients with Metastatic Gastro-Esophageal Junction/Gastric Cancer Treated with PD-1/PD-L1 Immune Checkpoint Inhibitors. Targ Oncol 15, 327–336 (2020). https://doi.org/10.1007/s11523-020-00723-z

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